Bleeding and thrombotic disorders are characterized by significant phenotypic variability. Over the last decade important advances have been made in the understanding of the molecular basis of these disorders;however a large portion of the observed variability remains unknown. Since excessive bleeding represents a significant medical issue with impressive morbidity and mortality, discovering new biomarkers of bleeding could have a very significant public health impact. Current assays for the diagnosis of bleeding disorders have limitations, particularly for the identification of mild to moderate bleeding and the discrimination of common variations in the hemostatic system. Also, quantifying clinical bleeding is extremely difficult. Therefore, a method that shows high sensitivity and specificity is highly desirable. We propose to develop a high-throughput microfluidic flow assay to quantify platelet adhesion, aggregation and fibrin deposition in blood samples of healthy individuals and individuals with established bleeding disorders. This study will represent the largest analysis to date of microfluidic assays in the clinical setting. We will correlate the results of these assays with current clinical and laboratory measures of bleeding phenotypes. It is our long term goal to develop a highly sensitive and specific method to determine the hemostatic potential of individuals with bleeding disorders. PUBLIC HEALTH RELEVANCE: It important to understand why some people bleed more than others. Currently, there are no methods that can accurately predict this problem. We are trying to develop a system where we can diagnose bleeding disorders and eventually predict risk for bleeding for example during surgery.